title: The dihydrofolate reductase-thymidylate synthetase gene in the drug resistance of malaria parasites.
abstract: Resistance to antifolate drugs such as pyrimethamine is widespread among malaria parasites of the most pathogenic species Plasmodium falciparum. These drugs inhibit the dihydrofolate reductase activity of the dihydrofolate reductase-thymidylate synthetase (DHFR-TS) bifunctional enzyme. This review examines work done to characterize the enzyme, the cloning of plasmodial DHFR-TS genes, chromosomal mapping studies of these genes by pulsed-field gel electrophoresis, and the structural insights into the mechanism of drug resistance that have been gained by comparing genes from drug-sensitive parasites with those from drug-resistant strains that have arisen in the field or after experimental induction.
authors.affiliation: Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology (UMIST), U.K.
authors.forename: J E
authors.initials: JE
authors.lastname: Hyde
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase